Chemokines Induced by Infection of Mononuclear Phagocytes with Mycobacteria and Present in Lung Alveoli during Active Pulmonary Tuberculosis
The capacity of Mycobacterium tuberculosis (MTB) to induce production of chemokines with known ch... more The capacity of Mycobacterium tuberculosis (MTB) to induce production of chemokines with known chemotactic activity for monocytes and lymphocytes, the cellular building blocks of granulomas, was investigated. These chemokines included regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha). MTB stimulated production of MCP-1 and MIP-1alpha by blood monocytes (MN) and alveolar macrophages (AM). MTB infection of MN and AM stimulated release but not production of RANTES. AM produced or released significantly higher levels than MN of RANTES (by 2.1-fold), MCP-1 (by 6.9-fold), and MIP-1alpha (by 5. 5-fold) (P < 0.05 for each). This study also confirmed that MTB-infected AM produce the chemokine interleukin (IL)-8. MTB infection of AM resulted in increased steady-state expression of messenger RNA (mRNA) for MCP-1 and MIP-1alpha and minimal increased expression of RANTES mRNA. Both an avirulent (H37Ra) and a virulent (H37Rv) strain of MTB and purified protein derivative of H37Rv but not latex beads induced production of chemokines. Supernatants of MTB-infected cells demonstrated chemotactic activity for both monocytes and lymphocytes partially inhibitable by neutralizing antibodies against the chemokines studied. Bronchoalveolar lavage fluid from patients with active pulmonary tuberculosis as compared with healthy control subjects contained increased levels of RANTES (by 8-fold), MCP-1 (by 2.7-fold), and IL-8 (by 8.9-fold) (P < 0.05), but not MIP-1alpha, as compared with healthy control subjects. Thus, multiple chemokines may be involved in recruitment of cells for granuloma formation in tuberculosis.
Erwinia chrysanthemi is a phytopathogenic bacterium causing soft rot disease in several agricultu... more Erwinia chrysanthemi is a phytopathogenic bacterium causing soft rot disease in several agricultural products. Conventional techniques used in the control of this phytopathology have serious limitations due to the emergence of resistant strains and the undesirable effect on the environment of chemical treatments. In this work, we report the isolation of an actinomycete strain from a Moroccan biotope that inhibits the growth of Erwinia chrysanthemi 3937VIII. PCR amplification and DNA sequencing of the 16 S ribosomal RNA gene allowed the identification of this strain as Streptomyces cinereoruber. The concentrated culture supernatant of this actinomycete strain exhibited activity against the growth of Erwinia chrysanthemi 3937VIII and two Gram-positive bacteria, Staphylococcus aureus and Bacillus amylolitiquefaciens, but had no effect on other Gram-negative bacteria tested (Erwinia carotovora 197stp R, Escherichia coli TG1 and Pseudomonas sp.), suggesting that this actinomycete strain secretes into the extracellular medium a substance that inhibits selectively the growth of other bacteria, especially the phytopathogenic Erwinia chrysanthemi 3937VIII. The antibacterial activity of Streptomyces cinereoruber found in this study highlights the importance of actinomycetes strains as candidates for the biological control of pathogenic bacteria. The identification and characterization of the active substance would open the way for further technological and therapeutic investigations.
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Papers by Zahra Mohamed